Many cytokines and growth factors which regulate cell differentiation, and in a pathological setting can cause cell transformation initiate their activities by binding to specific receptors on the cell surface. After binding to a given receptor, a cascade of events is initiated which results in the rapid induction in the expression of cellular genes. The new protein products which are synthesized a result of these early events can then exert phenotypic changes expressed by the cell. This lab is interested in understanding the very early events that occur after cytokines such as interferons bind to their cell surface receptors and transmit signals to the cell nucleus which stimulate the expression of cellular genes. Understanding the events which control these signaling cascades has progressed very rapidly over the past two years due to contributions from several labs including our own. Now that the general outlines of this process have been defined, and some of the proteins which regulate signaling are known, it will be possible in the near future to specifically modify these cascades for therapeutic benefits. Since many of the growth factors and cytokines that are being used therapeutically use the general signaling mechanisms outlined above, review of these products both now and in the future will require individuals who are very familiar with the most recent advances in this rapidly evolving area of growth factor biology. The research being done in this lab allows us to not only contribute to our understanding in this area, it provides us with the expertise to make rational evaluations as to how these products can be used therapeutically. There are currently 5 approved interefrons and many as the subject of pending PLAs and INDs. These research projects help us understand how interefrons might be better used clinically for approved and new indications and help us understand the mechanism of interferon toxicities.